This invention relates to the preparation of N-acetyl-p-aminophenol by acetylation of p-aminophenol in an aqueous medium, and more particularly, to an improved process for the recovery of N-acetyl-p-aminophenol from the aqueous medium.
The analgesic N-acetyl-p-aminophenol, commonly known in the art as acetaminophen or "APAP", is commercially prepared by reaction of p-aminophenol ("PAP") with acetic anhydride in an acidic aqueous medium. p-Aminophenol is conventionally prepared by catalytic hydrogenation of nitrobenzene in a mineral acid system. After purification of the reaction product for removal of residual impurities such as 4,4'-diaminodiphenyl ether, the p-aminophenol is precipitated as its alkali metal salt by addition of a caustic solution or an alkali metal carbonate or bicarbonate. The precipitated product is redissolved in acetic acid solution and acetic anhydride added for acetylation of the PAP to APAP.
In the co-pending and co-assigned application of William R. Clingan et al, Ser. No. 251,461, filed Apr. 20, 1981, a process is described for extractive removal of 4,4'-diaminodiphenyl ether and related impurities from the aqueous reaction product obtained upon catalytic hydrogenation of nitrobenzene to PAP. Use of this process reduces the level of impurities to be dealt with in the acetylation of PAP to APAP. Irrespective of what process is used for preparation and refining of the intermediate PAP, APAP is produced by acetylation of PAP in an acidic aqueous solution.
APAP is recovered from the reaction solution by crystallization and filtration or centrifugation, yielding a mother liquor that remains saturated in APAP and contains a substantial proportion of acetic acid. Unless this crude mother liquor is subjected to further processing for recovery of at least a portion of the APAP and acetic acid remaining in the solution, a substantial yield loss may be suffered. Commercially acetic acid has been recovered by distillation of the crude mother liquor, leaving a residue which may be crystallized for recovery of a second crop of APAP crystals. However, in this commercial practice, the acetic acid fraction recovered typically has a strength of only about 20% by weight to 25% by weight which limits the uses to which it can be put, and its value. Color bodies in the mother liquor are concentrated in the distillation residue and tend to impart an undesirably strong color to the second crop of APAP crystals. Additionally, corrosion problems may be encountered in distillation of the mother liquor due to the presence of sulfur dioxide released from the bisulfate salts conventionally added to an APAP crystallization system to protect the APAP product against air oxidation.